1. Field of the Invention
The present invention relates to determining whether thrombolysis therapy would be beneficial to an acute ischemic stroke patient, and more particularly, to methods and apparatuses for making such a determination.
2. Background of the Related Art
Ischemic strokes are the third leading cause of death after cardiovascular diseases and cancers. In the United States alone, strokes affect over 750,000 patients each year, among whom one-third will be permanently disabled. Thus, strokes represent one of the leading causes of disability.
Viability of the cerebral tissue depends on cerebral blood flow. During a stroke, a portion of brain tissue known as the ischemic lesion is deprived of sufficient blood flow due to an arterial occlusion (blood clot). The ischemic lesion includes two parts: the infarct and the penumbra. The infarct comprises brain tissue in which blood flow is so drastically reduced that the brain cells do not recover. The penumbra surrounds the infarct and corresponds to a transitional zone in which brain cells are endangered, but not yet irreversibly damaged.
A major difference between penumbra and infarct relates to cerebral perfusion autoregulation. Complex autoregulation processes ensure both the adjustment of cerebral blood flow to local neuronal activity and cerebral blood flow stability despite changes in systemic arterial pressure. Brain vascular autoregulation notably allows for a vascular dilatation when the systemic pressure tends to lower, in order to keep a constant cerebral blood flow. This vascular dilatation leads in turn to an increased cerebral blood volume, at least in salvageable penumbra. In infarcted cerebral gray matter, autoregulation mechanisms are altered, and both cerebral blood flow and cerebral blood volume are diminished.
Early after a cerebral arterial occlusion occurs, reversible inhibition or penumbra occurs in the territory of cerebral tissue usually perfused by the affected artery. With time, irretrievable infarction, however, progressively replaces the penumbra. The replacement rate varies according to the collateral circulation level.
Thrombolysis therapy using blood clot dissolution drugs has been introduced to save ischemic but viable cerebral tissue. The application of this therapy relies on the time interval between the onset of symptomatology and the native cerebral CT findings.
However, if thrombolysis therapy is used on a patient where extensive oligemia in the territory of an occluded cerebral artery, where there is limited penumbra area, the therapy would yield little to no benefit and even increases the risk of intracranial bleeding.
Accordingly, the present invention addresses all of the above concerns and provides a method and apparatus for determining whether thrombolysis therapy would be beneficial to an acute ischemic stroke patient. The method is independent from methods currently used in perfusion-CT scans.
Using perfusion-CT examinations, the present invention provides a valuable tool in the early management of acute stroke patients, in their admission evaluation and in the choice whether to include them or not in a thrombolysis protocol.
Specifically, perfusion-CTs provide a map of cerebral blood flow, cerebral blood volume and mean transit time maps. Using a predetermined algorithm according to the present invention, the ischemic cerebral area (penumbra+infarct) is determined and mapped. After the penumbra and infarct maps are determined, they are used to calculate a potential recuperation ratio (PRR), which in effect determines whether an acute stroke patient is a candidate for thrombolysis therapy.
The present invention determines the size and location of infarct and penumbra and produces a visual image (map) of the result. These infarct and penumbra images are calculated from cerebral blood flow (CBF) and cerebral blood volume (CBV) measurements of a perfusion-CT.
The ischemic lesion (penumbra+infarct) is determined where said measurements of cerebral blood flow is a predetermined amount less than normal cerebral blood flow of an unaffected corresponding portion of the brain. Within this ischemic lesion, infarct corresponds to areas where cerebral blood volume is less than a predetermined amount and penumbra corresponds to areas where cerebral blood volume is more than this predetermined amount.
The present invention can also be used to evaluate the relative extent of the calculated infarct and penumbra to each other, thus allowing to calculate an index, called for instance potential recuperation ratio (PRR) (or Lausanne stroke index or Wintermark stroke index). This index, with adequate thresholds, can be used for determining whether an acute stroke patient is a candidate for thrombolysis therapy.
Accordingly, in a first aspect of the present invention, a method for creating a penumbra and infarct image of the brain of an acute stroke patient includes obtaining measurements of the cerebral blood flow and cerebral blood volume of the brain of an acute stroke patient and determining ischemic areas of the brain. The ischemic areas of the brain are determined where the measurements of cerebral blood flow is a predetermined first value less than normal cerebral blood flow of an unaffected corresponding portion of the brain. The method also includes creating a penumbra and infarct map comprising penumbra areas of the ischemic areas of the brain using the measurements of cerebral blood volume, where penumbra areas correspond to ischemic areas of the brain having cerebral blood volume greater than said predetermined second value. The image created according to the above method may also include infarct areas of the ischemic areas of the brain, resulting in a penumbra-infarct map of the brain. The infarct areas correspond to ischemic areas of the brain where cerebral blood volume is less than the predetermined second value.
In another aspect of the present invention, a map of the brain of a stroke patient includes penumbra areas corresponding to areas of the brain having a cerebral blood volume of greater than a predetermined value. The map may also include infarct areas corresponding to areas of the brain having a cerebral blood volume of less than the predetermined value.
In yet another aspect of the present invention, an apparatus for creating a penumbra and infarct image of the brain of an acute stroke patient includes measuring means for obtaining measurements of the cerebral blood flow and cerebral blood volume of the brain of an acute stroke patient, and determining means for determining ischemic areas of the brain. The ischemic areas are determined where the measurements of cerebral blood flow are less than a predetermined first value. The apparatus also includes mapping means for creating a penumbra and infarct image comprising penumbra areas of the ischemic areas of the brain using the measurements. The penumbra areas correspond to areas of the brain having cerebral blood volume greater than the predetermined second value. The infarct areas correspond to areas of the brain having cerebral blood volume less than the predetermined second value.
In yet another aspect of the present invention, a computerized method for creating a penumbra and infarct image of the brain of an acute stroke patient includes storing a plurality of measurement data corresponding to the cerebral blood flow and cerebral blood volume of the pathological hemisphere of the brain of an acute stroke patient in a first database, processing measurement data to determine ischemic areas of the brain by querying the database for measurement data corresponding to cerebral blood flow being less than a first value, where a result of the query is stored as ischemic data in the database. The method also includes processing the ischemic data to determine penumbra areas of the ischemic areas, where the penumbra areas correspond to ischemic data where cerebral blood volume greater than the second value and ischemic data corresponds to the penumbra areas is stored as penumbra data. With this method, infarct areas may be included in the penumbra and infarct image, with the infarct areas corresponding to ischemic data where cerebral blood volume is less than the second value and ischemic data corresponding to the infarct areas is stored as infarct data in the database.
In yet another aspect of the present invention, a medical diagnostic apparatus for determining whether a stroke patient will benefit from the use of thrombolysis therapy includes storing means for storing a plurality of measurement data corresponding to the cerebral blood flow and cerebral blood volume of the pathological hemisphere of the brain of an acute stroke patient in a first database, processing means for:
processing measurement data to determine ischemic areas of the brain by querying the database for measurement data corresponding to cerebral blood flow that is less than a first value, where a result of said query is stored as ischemic data in said database;
for processing the ischemic data to determine infarct areas and penumbra areas of the ischemic areas, where infarct areas correspond to ischemic data where cerebral blood volume is less than a second value and penumbra areas correspond to ischemic data where cerebral blood volume greater than the second value. Ischemic data corresponding to infarct areas is stored as infarct data in the database and ischemic data corresponding to penumbra areas is stored as penumbra data; and
for processing the infarct data and the penumbra data to determine a ratio that the penumbra size comprise the total of the infarct size and the penumbra size. When the ratio is greater than a predetermined third value, the stroke patient is a candidate for thrombolysis therapy.
In yet another aspect of the present invention, computer readable media having computer-executable instructions for performing the above-recited methods is provided.
In still yet another aspect of the present invention, computer readable media having stored thereon a data structure including a first field containing measurement data corresponding to the cerebral blood flow and cerebral blood volume of the pathological hemisphere of the brain of an acute stroke patient, a second field comprising ischemic data corresponding to ischemic areas of the brain, a third field comprising infarct data corresponding to infarct areas of the brain, a fourth field comprising penumbra data corresponding to penumbra areas of the brain, and a fifth field comprising ratio data comprising a ratio of penumbra size to the total of infarct size and penumbra size.
The present invention provides preferred thresholds for determining whether an acute stroke patient is a candidate for thrombolysis therapy based on infarct and penumbra maps determined by cerebral blood flow and cerebral blood volume maps of a perfusion-CT.